Although devices containing silicone have been in widespread clinical use for over 25 years, little is known about their safety. Reports of autoimmune and connective tissue disorders following implantation of silicone devices have induced concern among some physicians about a causal relationship, although no adequate data exist to refute or support such claims. Because investigations of drug-induced autoimmune and connective tissue disorders have documented clinical, serologic and immunogenic differences in these patients compared to those who develop the same "idiopathic diseases" without exposure to the offending drugs, we are studying such differences in myositis patients with and without silicone prostheses. Current data on 13 white women who developed myositis after silicone exposure show significant differences in clinical, serologic, and immunogenetic features compared to 76 sex- and race-matched myositis patients without silicone exposure and compared to normal controls. These findings are the first to suggest that the presence of certain immune response genes may identify a group of patients at increased risk for the development of connective tissue disease after silicone exposure. Further studies of these and other patients with silicone- associated autoimmune or rheumatic diseases should allow a better understanding of such genetic risk factors, and may allow dissection of pathogenetic mechanisms leading to these diseases.